Patients with HIV infection are at risk for increasing viral replication, CD4+ cells declines, disease progression and death, if untreated. Although combination regimens with zidovudine, lamivudine (3TC) and indinavir (IDV) in patients with advanced HIV disease are associated with improved disease-free survival, the majority of patients have detectable virus as measured by HIV-1 RNA levels and HIV-1 culture. Therefore, long-term therapy is likely to be associated with disease progression due to incomplete suppression of HIV replication and emergence of viral resistance. Combination regimens with two protease inhibitors may be highly advantageous and may afford enhanced viral suppression and delayed viral resistance when given with reverse transcriptase inhibitors. Several studies suggest varying pharmacokinetic drug interactions between saquinavir (SQV) and either ritonavir (RTV) or nelfinavir (NFV) and IDV and either NFV or RTV that result in better plasma drug concentrations of the various component drugs. Preliminary data also suggest that combination protease inhibitors are associated with substantial suppression of the HIV replication, as measured by the proportion with plasma HIV RNA levels below the level of quantitation in the circulation and are well tolerated. Combination three-drug regimens with non-nucleoside reverse transcriptase inhibitors (NNRTI) also result in profound suppression of HIV replication. Based on these data, it may be possible to generate more potent antiretroviral drug regimens that will result in more durable suppression of viral replication, without the emergence of viral resistance. This study is a phase III, randomized, open label, controlled trial of either NFV or EFZ with IDV/3TC/ZDV vs IDV/3TC/ZDV alone. A total of 444 subjects with HIV infection, < 200 CD4 cells/mm3 or > 100,000 HIV RNA copies/ml of plasma and limited or no prior antiretroviral treatment will be enrolled and randomly assigned to:3TC 150 mg/ZDV 300 mg BID + IDV 800 mg TID vs 3TC 150 mg/ZDV 300 mg BID + IDV 1000 mg TID + EFZ 600 mg QD vs 3TC 150 mg/ZDV 300 mg BID + IDV 1000 mg BID + NFV 1250 mg BID. Subjects will be followed for 72 weeks beyond the enrollment of the last subject. Clinical evaluations and routine laboratory tests will be done at screeening, and at Weeks 4,8 and every 8 weeks thereafter. CD4/CD8 cell counts and plasma HIV RNA measurement will be done at pre-entry, entry (Day 0), and at Weeks 4,8 and every 8 weeks thereafter and at the time of virologic failure or relapse PBMCs, HIV qualitative macro-culture, and population pharmacokinetics will be performed at selected timepoints.